Parkinson’s disease is a progressive neurological condition that affects more than 1 million people in the United States and over 10 million worldwide. The disease causes a wide range of debilitating symptoms, including tremors, difficulty with movement, sleep problems, and cognitive decline. Current treatment options, such as long-term medications and invasive deep brain stimulation (DBS), can reduce symptoms, but they do not stop the disease from advancing or offer a cure.
An international research team led by China’s Changping Laboratory, working alongside Washington University School of Medicine in St. Louis and other partners, has identified a specific brain region linked to the central features of Parkinson’s disease. The researchers found that a brain network called the somato-cognitive action network (SCAN) plays a critical role in the disorder. When this network was targeted using a non-invasive experimental technique known as transcranial magnetic stimulation (TMS), patients experienced more than twice the symptom improvement seen when nearby brain areas were stimulated instead.
The findings, published Feb. 4 in Nature, challenge long-standing views of Parkinson’s disease and point toward a new era of more precise and targeted treatment approaches.
“This work demonstrates that Parkinson’s is a SCAN disorder, and the data strongly suggest that if you target the SCAN in a personalized, precise manner you can treat Parkinson’s more successfully than was previously possible,” said co-author Nico U. Dosenbach, MD, PhD, the David M. & Tracy S. Holtzman Professor of Neurology at WashU Medicine. “Changing the activity within SCAN could slow or reverse the progression of the disease, not just treat the symptoms.”
Understanding SCAN and Its Role in Movement and Thought
Dosenbach first described the SCAN in Nature in 2023. The network is located within the motor cortex, the area of the brain responsible for controlling body movements. Its job is to translate planned actions into physical motion and then monitor how those actions unfold. Because Parkinson’s disease affects far more than movement alone, influencing digestion, sleep, motivation, and thinking, senior author Hesheng Liu, PhD, joined forces with Dosenbach to investigate whether disruptions in SCAN could explain the disease’s broad range of symptoms and serve as a treatment target.
To test this idea, Liu’s team analyzed brain imaging data from more than 800 participants across multiple research centers in the United States and China. The group included people with Parkinson’s disease receiving DBS or non-invasive therapies such as transcranial magnetic stimulation, focused ultrasound stimulation, and medications. Healthy volunteers and individuals with other movement disorders were also included for comparison.
Abnormal Brain Connectivity Revealed
The analysis showed that Parkinson’s disease is marked by excessive connectivity between the SCAN and the subcortex, a brain region involved in emotion, memory, and motor control. Across all four therapies examined in the study, treatments worked best when they reduced this overconnection. Restoring a more balanced relationship between these regions helped normalize activity in the brain circuit responsible for planning and coordinating actions.
“For decades, Parkinson’s has been primarily associated with motor deficits and the basal ganglia,” the part of the brain that controls muscle movements, Liu said. “Our work shows that the disease is rooted in a much broader network dysfunction. The SCAN is hyperconnected to key regions associated with Parkinson’s disease, and this abnormal wiring disrupts not only movement but also related cognitive and bodily functions.”
Precision Treatment Shows Early Promise
Building on these insights, the researchers developed a precision treatment system designed to target the SCAN without surgery and with millimeter-level accuracy. The approach uses transcranial magnetic stimulation, which delivers magnetic pulses to the brain through a device placed on the head. In a clinical trial, 18 patients who received SCAN-targeted stimulation showed a 56% response rate after two weeks. By comparison, only 22% of 18 patients who received stimulation to nearby brain regions improved, representing a 2.5-fold increase in effectiveness.
“With non-invasive treatments, we could start treating with neuromodulation much earlier than is currently done with DBS” because they don’t require brain surgery, Dosenbach said.
He noted that more foundational research is still needed to understand how different parts of the SCAN contribute to specific Parkinson’s symptoms.
Looking ahead, Dosenbach plans to launch clinical trials with Turing Medical, a WashU Medicine startup he co-founded. These studies will test a non-invasive therapy that uses surface electrode strips placed over SCAN regions to address gait problems in people with Parkinson’s disease. He also intends to explore low-intensity focused ultrasound as another non-invasive method for altering SCAN activity using acoustic energy.
This work was supported by the Changping Laboratory, the U.S. National Institutes of Health (MH096773, MH122066, MH121276, MH124567, NS129521, NS088590, R01NS131405, U01NS098969, and U01NS117836), the National Natural Science Foundation of China (81527901, 81720108021, 81971689, 31970979, and 82090034), the National Key R&D Program of China (2017YFE0103600), the Intellectual and Developmental Disabilities Research Center; the Kiwanis Foundation; the Washington University Hope Center for Neurological Disorders; and the Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health of Anhui Province (2020xkjT05). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
H.L. is the chief scientist of Neural Galaxy Inc. L.L. serves on the scientific advisory board for Beijing Pins Medical Co., Ltd and are listed as inventors in issued patents and patent applications on the deep brain stimulator used in this work. N.U.F.D. has a financial interest in Turing Medical Inc. and may financially benefit if the company is successful in marketing FIRMM motion monitoring software or BullsAI neuromodulation targeting software or PACE neuromodulation systems. E.M.G. and N.U.F.D. may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and licensed to Turing Medical Inc. N.U.F.D. is a co-founder of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. S.L. consults for Iota Biosciences. P.A.S. receives support from Medtronic and Boston Scientific for fellowship education.
